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Jemds.com Case Report

Medication Related Osteonecrosis of

Prasanthi Sitaraman1, Arvind Muthukrishnan2

1Department of Oral Medicine and Radiology, Saveetha Dental College, Tamilnadu, India. 2Department of Oral Medicine and Radiology, Saveetha Dental College, Chennai, Tamilnadu, India.

PRESENTATION OF CASE

A 41 year old female patient reported with the complaint of pain in the right posterior Corresponding Author: mandibular region for the past 5 months. History revealed that patient was diagnosed Dr. Prasanthi Sitaraman. with breast before 4 years following which she underwent mastectomy, Department of Oral Medicine and radiotherapy and chemotherapy. PET / CT taken post chemotherapy showed Radiology, Saveetha Dental College, Saveetha Institute of Medical and Technical metastasis to the lumbar spine for which she was prescribed I.V. to Sciences (SIMATS), 162, Poonamallee High be administered every 3 months. Patient was under I.V. zoledronic acid for a total of Road, Chennai - 600077, Tamilnadu, India. 36 months. E-mail: [email protected] Patient underwent surgery for extraction of impacted lower third molar before 7 months. The extraction site did not completely heal following which the tooth DOI: 10.14260/jemds/2020/602 adjacent to the extraction site became mobile. The mobile tooth was also extracted before 5 months following which she developed pain and swelling in the region. How to Cite This Article: Patient was diagnosed with and underwent curettage and Sitaraman P, Muthukrishnan A. Medication related osteonecrosis of jaw. J Evolution antiseptic dressing for 2 months. However, there was no reduction in pain. Pain was Med Dent Sci 2020;9(37):2770-2772, DOI: gradual in onset, continuous, gnawing, in the extraction site, aggravated by 10.14260/jemds/2020/602 mastication and relieved by medication. On clinical examination, non – healing extraction socket was evident in 47, 48 Submission 13-06-2020, region. A single, oval ulcer measuring about 0.5 cm * 0.5 cm was evident in the medial Peer Review 07-08-2020, surface of the retro molar area in 48 region. The margins of the ulcer was well – Acceptance 13-08-2020, Published 14-09-2020. defined and the floor was covered with granulation tissue with erythematous surrounding mucosa. No discharge is evident from the ulcer. On palpation, the ulcer Copyright © 2020 Prasanthi Sitaraman et is tender. The floor of the ulcer revealed necrotic bone (Figure 1). al. This is an open access article distributed The patient was subsequently subjected to Orthopantomogram (OPG) and under Creative Commons Attribution Computed tomography (CT) (Figure 2). OPG shows missing 47, 48 and loss of alveolar License [Attribution 4.0 International (CC bone and extending from the distal surface of 46 and posteriorly to the retromolar BY 4.0)] region, inferiorly to about 2 mm from the mandibular canal. The affected bone has irregular margins and comparatively radiolucent to the surrounding bone on the posterior margin. The CT – axial, coronal, sagittal sections with 3D reconstruction showed post-operative bone defect in the lower right second and third molar region from the previous curettage. In consultation with the physician, intravenous was discontinued. Antibiotics clindamycin (300 mg, B.I.D.) was coupled with pentoxiphylline (400 mg, O.D.) with supplementary povidone iodine and gluconate mouth gargle was prescribed. The exposed bone was subsequently surgically removed after 15 days of medical management (Figure 3). Based on the chief complaint, medical history and radiographic findings, a diagnosis of stage 2 Medication Related Osteonecrosis of Jaw (MRONJ) was given. The patient is under regular follow-up. Anti-resorptive drugs are those drugs that reduce bone loss by decreasing osteoplastic . They are used in the treatment of various medical conditions, including , multiple myeloma, and breast cancer with skeletal metastasis, because they reduce bone pain, hyperkalaemia, and the risk of pathologic fractures. There are 5 classes of antiresorptive drugs, of which are increasingly associated with Osteonecrosis of jaw. This condition was named as Bisphosphonate related osteonecrosis of jaw (BRONJ), later renamed as Medication related osteonecrosis of jaw (MRONJ) following identification of non-bisphosphonate related aetiology such as antiangiogenic agents such as bevacizumab, aflibercept and sunitinib.

J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 37 / Sept. 14, 2020 Page 2770

Jemds.com Case Report

This case report describes a 41-year-old female patient on zoledronic acid therapy following bone metastasis from breast cancer who developed osteonecrosis of jaw following extraction of right lower wisdom teeth. Careful history taking to review medication in oncology patients with history of chemotherapy (antiresorptive drugs) and liaison with medical oncologist prior to any invasive dental treatment on these patients with bisphosphonates / / antiangiogenic drugs is absolutely necessary to prevent the occurrence of consequences such as MRONJ. Role of oral medicine physicians in prevention and treating osteochemonecrosis is inevitable as early prevention and accurate treatment increases quality of life in these groups of patients. Antiresorptive drugs are osteotropic agents used for their ability to prevent bone resorption in patients with osteoporosis, metabolic bone diseases and hypercalcemia. The classes of antiresorptive drugs are bisphosphonates, oestrogens, selective oestrogen receptor modulators, calcitonin, and monoclonal antibodies. There are three generations of bisphosphonates, most potent of these drugs are the second and the third generation - alendronate and zoledronate1. Other common indications for the use of BPNs is metastatic cancer of bone. First described by Marx in 2003, osteonecrosis of jaw is the most frequently reported adverse effect of BPNs2. The terms bisphosphonate - related osteonecrosis of the jaw (BRONJ) and antiresorptive agent related ONJ (ARONJ) has been advocated. The AAOMS position paper (2014) favours the use of the term medication-related osteonecrosis of the jaw (MRONJ) after identification of other drugs like anti – angiogenic drugs as the cause of osteonecrosis3. MRONJ is considered a severe adverse drug reaction, consisting of progressive bone destruction in the maxillofacial region of patients. Patients under zoledronic acid and denosumab have shown to have increased risk of developing MRONJ than other antiresorptive drugs3. This case study illustrates a 41-year-old female patient under I.V. zoledronic acid who reported with jaw pain post extraction of wisdom tooth.

Figure 2. OPG and CT Sections Showing Affected Bone in the Region Distal to 46

Figure 1. Floor of the Ulcer Revealing Necrotic Bone Figure 3. Post-Operative Photograph Following Surgical Curettage of the Necrotic Bone

J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 37 / Sept. 14, 2020 Page 2771

Jemds.com Case Report

prior to any invasive dental treatment on these patients and DISCUSSION treating with bisphosphonates / denosumab / antiangiogenic drugs is absolutely necessary to prevent the occurrence of MRONJ is a consequence of use of antiresorptive drugs and consequences such as MRONJ. Role of oral medicine physicians antiangiogenic drugs for varied therapeutic indications. The in prevention and treating osteochemonecrosis is inevitable as pathophysiology is not well understood. However, multiple early prevention and accurate treatment increase the quality hypothesis has been put forward to elucidate the localization of life in these groups of patients. to the and not the other of the body. These include altered remodelling, trauma, suppression of osteoclastic Financial or Other Competing Interests: None. activity, inhibition of angiogenesis, decreased vascularity to the jaw bone and suppression of immunity due to previous treatments for treating cancer.4 Risk factors like the drug, REFERENCES mode of administration, length of therapy, age and gender of the patient, other co – morbidities, local factors like trauma from dentures, inflammatory disease have to be considered. [1] Drake MT, Clarke BL, Khosla S. Bisphosphonates: Multiple studies have reported that in about 52 – 61 % of cases, mechanism of action and role in clinical practice. Mayo acts as trigger for MRONJ which is similar to Clin Proc 2008;83(9):1032-45. that of our case.5,6 Detailed history with the duration of [2] Marx RE. Pamidronate (Aredia) and zoledronate treatment with antiresorptive and antiangiogenic medication (Zometa) induced avascular of the jaws: a has to be recorded prior to any dental procedure. growing epidemic. J Oral Maxillofac Surg Communication with the oncologist / physician is 2003;61(9):1115-7. unquestionably needed to prevent complications such as [3] Ruggiero SL, Dodson TB, Fantasia J, et al. American MRONJ.7 association of oral and maxillofacial surgeons position Case definition of BRONJ / ARONJ / MRONJ has not paper on medication-related osteonecrosis of the jaw- changed since the AAOMS position paper, 2009.3,8 Presence 2014 update. J Oral Maxillofac Surg 2014;72(10):1938- current or previous treatment with a bisphosphonate, exposed 56. bone in the maxillofacial region that has persisted for more [4] Rosella D, Papi P, Giardino R, et al. Medication-related than 8 weeks and no history of radiation therapy to the jaws is osteonecrosis of the jaw: clinical and practical guidelines. characteristic for MRONJ. Multiple staging systems have been J Int Soc Prev Community Dent 2016;6(2):97-104. proposed for MRONJ based on clinical and radiographic [5] Kajizono M, Sada H, Sugiura Y, et al. Incidence and risk features as at risk, stage 0, 1, 2 and 3 4. factors of osteonecrosis of the jaw in advanced cancer The medical management of MRONJ is aimed to control patients after treatment with zoledronic acid or infection, minimize necrosis progression and promote tissue denosumab: a retrospective cohort study. Biol Pharm Bull healing.9 Use of systemic antibiotics and oral antiseptic rinses 2015;38(12):1850-5. such as Chlorhexidine gluconate are recommended. Use of [6] Vahtsevanos K, Kyrgidis A, Verrou E, et al. Longitudinal both these strategies along Vitamin E led to the healing of the cohort study of risk factors in cancer patients of necrosed bone in our patient. Other treatment options bisphosphonate-related osteonecrosis of the jaw. J Clin available are hyperbaric oxygen therapy, low level laser Oncol 2009;27(32):5356-62. therapy, ozone therapy and platelet rich plasma in post- [7] Kalra S, Jain V. Dental complications and management of surgical wound.10 Surgical treatments include patients on bisphosphonate therapy: a review article. J sequestrectomy, debridement, resection, immediate Oral Biol Craniofac Res 2013;3(1):25-30. reconstruction. Surgical treatment may also include extraction [8] Ruggiero SL, Dodson TB, Assael LA, et al. American of teeth within exposed necrotic bone. In the case in question, association of oral and maxillofacial surgeons position sequestrectomy was done followed by medical management paper on bisphosphonate-related osteonecrosis of the with antibiotics and antiseptic mouth rinse. jaws--2009 update. J Oral Maxillofac Surg 2009;67(5 Suppl):2-12. [9] Beth-Tasdogan NH, Mayer B, Hussein H, et al.

Interventions for managing medication-related CONCLUSIONS osteonecrosis of the jaw. Cochrane Database Syst Rev 2017;10(10):CD012432. Osteonecrosis of jaw has constantly been researched on and [10] Heggendorn FL, Leite TC, Cunha KSG, et al. has been renamed as BRONJ, ARONJ and MRONJ based on the Bisphosphonate-related osteonecrosis of the jaws: report medication responsible. Careful history taking to review of a case using conservative protocol. Spec Care Dentist medication in oncology patients with history of chemotherapy 2016;36(1):43-7. (antiresorptive drugs) and liaisoning with medical oncologist

J Evolution Med Dent Sci / eISSN - 2278-4802, pISSN - 2278-4748 / Vol. 9 / Issue 37 / Sept. 14, 2020 Page 2772